A phase II trial of trastuzumab (H) + capecitabine (X) as first-line treatment in patients (pts) with HER2-positive metastatic breast cancer (MBC)

Abstract

10615 Background: The addition of H to a taxane provides significant clinical benefit, including prolonged survival, in HER2-positive MBC. H adds little to the toxicity of taxanes alone. As monotherapy, X has consistently high activity and favorable safety. The addition of X to docetaxel extends survival in MBC. Preliminary data [Bangemann et al. 2000] indicated that the combination of H + X is effective and well-tolerated for intensively pretreated HER2-positive MBC (ORR 47%). The current study evaluated the efficacy and safety of H + X in first-line MBC. Methods: 72 pts of a planned population of 100 pts were enrolled between Mar03 and Dec05. All pts had measurable (WHO criteria), HER2-positive (IHC 3+ or IHC 2+/FISH positive) and untreated MBC, KPS ≥60, and adequate organ function. H was administered as a 4mg/kg loading dose followed by 2mg/kg i.v. weekly (until disease progression) and X 1250mg/m2 bid d1–14 q3w (max 6 cycles). The primary endpoint was progression-free survival (PFS). Results: Baseline characteristics: median age 49 years (range 27–74), median KPS 90 (range 60–100). Principal tumor sites: lymph nodes (49%), lung (33%), liver (28%), breast (14%), thoracic wall (9%), chest (9%), other (12%). Prior treatment: surgery (77%), radiotherapy (21%), and adjuvant chemotherapy (58%), including anthracycline (35%), paclitaxel (7%), docetaxel (7%) and other (21%). 43 pts are evaluable for safety and efficacy. The remaining 29 pts are being analyzed. 6 pts received 3 cycles of H + X; the other 37 pts completed 6 cycles of treatment. 16 pts received H monotherapy after completing 6 cycles of H + X. 3 pts discontinued H due to disease progression. The most common grade 1/2 adverse events (AEs) were HFS (14%), neutropenia (14%), SGOT abnormality (16%), and SGPT abnormality (14%). Grade 3 HFS occurred in 4 pts (10%) with grade 3 myelosuppression in 1 pt (2%). AEs were mild and resolved in all pts. The overall response rate was 63%, including 5 CRs and 22 PRs. At a median follow-up of 6 months, median PFS has not been reached. Conclusions: The combination of H and X is a highly active and well-tolerated regimen for first-line treatment of HER2-positive MBC. Updated data will be presented. No significant financial relationships to disclose.